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Biomedical subjects

M M Lyons

Publications and source records attributed to M M Lyons.

30 records · Page 2Linked to original sources
PubMed1977

The effects of tolbutamide on the myocardium in experimental diabetes.

The effects of chronic tolbutamide treatment were examined in a diabetic animal model in which abnormal myocardial function and composition have previously been demonstrated. Eight diabetic dogs were given tolbutamide 250 mg/day orally and compared with seven untreated diabetics, five healthy dogs receiving tolbutamide, and eight normal controls. After one year, resting hemodynamic studies in the intact anesthetized state showed that treated diabetic dogs had a significantly higher left ventricular end-diastolic pressure of 12.1+/-1.3 mm Hg associated with normal end-diastolic volume, compared to 6.1+/-0.8 mm Hg in untreated diabetics (P less than 0.01) and 6.3+/-0.5 in normals. Stroke work and ejection fraction were similar to normals. Acute volume expansion revealed a larger rise of left ventricular end-diastolic pressure in treated and untreated diabetics than normals, without a significant stroke volume response in treated diabetics. Enhanced stiffness of myocardium appeared to be related to interstitial accumulation of periodic acid-Schiff staining material, further intensified in treated diabetics by triglyceride accumulation observed on electron microscopy and by chemical analysis. Thus treatment of diabetes with tolbutamide, despite improved glucose tolerance, effected further reduction of left ventricular function and altered morphology of myocardium.

Animals↗
PubMed1977

Evidence for cardiomyopathy in familial diabetes mellitus.

Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age. Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia. Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.

Adult↗
PubMed1976

Cardiovascular effects of long-term cigarette smoking and nicotine administration.

The nature of the cardiovascular risk in cigarette smokers has not been characterized. To compare the relative effects of long-term smoking and nicotine administration on the cardiovascular system, 18 month old beagle littermates were prepared with a permanent tracheostomy. They were classified into three groups: I, seven control dogs; II, nine dogs that smoked seven cigarettes/day; and III, eight dogs that received an equivalent amount of nicotine. After a period of up to 22 months, the animals were catheterized under anesthesia for assessment of left ventricular function and volumes by indicator-dilution technique. Heart rate, stroke volume, left ventricular end-diastolic pressure and volume and intraventricular conduction times did not differ significantly in the three groups. Left ventricular ejection fraction was 44 +/- 3 percent (mean +/- standard error of the mean) in the control group, 35 +/- 3 percent in the dogs that smoked cigarettes (P less than 0.05) and 27 +/- 3 percent in those given nicotine (P less than 0.01) despite similar values for end-diastolic variables in the three groups. The first derivative of left ventricular pressure (dP/dt) normalized for pre- and afterload was 2.4 +/- 0.2 cm/sec -1 in the control group, 1.41 +/- 0.12 in the cigarette-smoking group (P less than 0.005) and 1.34 +/-0.08 in the nicotine group (P less than 0.01). Although mean aortic pressure was significantly elevated in both the smoking (127 +/- mm Hg) and nicotine (127 +/- 10 mm Hg) groups, there was no significant correlation with the contractility indexes. Reduction of afterload to normal levels did not affect the abnormal ventricular performance. Hypertrophy, inflammation and abnormalities of cell ultrastructures were not present, and myocardial lipid and cation composition were normal. Since interstitial fibrosis was evident in both experimental groups, an alteration of elastic elements may be operative. These cardiovascular abnormalities appear to be predominantly dependent on the nicotine of cigarettes.

Animals↗
PubMed1975

Occupational lead nephropathy.

Among eight subjects suspected of excessive occupational exposure to lead, detailed examination of renal function identified abnormalities in four. Glomerular filtration rate was less than 87 ml/mim/1.73 m2 in one subject with asymptomatic renal failure, and in three subjects with preclinical renal dysfunction. In the subject with asymptomatic renal failure, chelation therapy increased the glomerular filtration rate, p-aminohippurate (PAH) extraction, the maximal PAH secretion rate (TmPAH) and improved proximal tubule ultrastructure, despite decreased renal plasma flow. This improvement in PAH transport was associated with correction of a proximal tubule defect in tritiated PAH uptake detected by section freeze-dry autoradiography of renal biopsy specimens. In three subjects, the etiologic diagnosis of lead-induced nephropathy was established by exclusion, but tubular dysfunction did not obviously exceed the reduction in blomerular filtration. Proximal tubule abnormalities were seen in each of the three patients who underwent biopsy. These studies suggest that lead nephropathy may be an important occupational hazard in the United States lead industry.

Aminohippuric Acids↗
PubMed1975

Acute myocardial infarction in toxic cardiomyopathy without coronary obstruction.

Confluent left ventricular scar without significant coronary obstruction has been found in alcoholic subjects at autopsy. To evaluate the pathogenesis, 12 patients with chronic alcoholism and severe precordial pain persisting 4-24 hours were observed clinically. Cardiac isoenzymes of lactic dehydrogenase rose in serum. ST segment was elevated in anterior or posterior ECG leads, and abnormal Q waves appeared. Hypertnesion and hypercholesterolemia were present in two (group B) but not in the ten (group A). The latter exhibited no significant obstructive disease, based on coronary angiography in seven survivors and postmortem examination of the remaining three. Clinical evidence, as well as the quantitative assessment of platelets, made arterial thromboembolism an unlikely cause for the symptoms. Neither hemotologic or systemic disease affecting myocardium was present. The morphology of the left ventricle in three autopsies was compared with that of patients with alcoholism who had no cardiac disease, cardiomyopathy, or an asymptomatic scar. All had accumulation of Alcian positive glycoprotein in the interstitium. The patients with cardiac disease also had interstitial fibrosis which was characterized, particularly in the acute infarction group, by concentric periarterial fibrosis. Restriction of coronary vasodilation by this process during periods of high blood flow requirements was postulated as a basis for infarction.

Adult↗
PubMed1974

Myocardial function and lipid metabolism in the chronic alcoholic animal.

In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium. To evaluate myocardial lipid metabolism, [1-(14)C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced (14)CO(2) production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [(14)C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic.

Alcoholism↗